Department of Pharmaceutical Biochemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688, Kraków, Poland.
Cancer Chemother Pharmacol. 2024 Aug;94(2):123-139. doi: 10.1007/s00280-024-04693-1. Epub 2024 Jul 4.
Aclarubicin (aclacinomycin A) is one of the anthracycline antineoplastic antibiotics with a multifaceted mechanism of antitumor activity. As a second-generation drug, it offers several advantages compared to standard anthracycline drugs such as doxorubicin or daunorubicin, which could position it as a potential blockbuster drug in antitumor therapy. Key mechanisms of action for aclarubicin include the inhibition of both types of topoisomerases, suppression of tumor invasion processes, generation of reactive oxygen species, inhibition of chymotrypsin-like activity, influence on cisplatin degradation, and inhibition of angiogenesis. Therefore, aclarubicin appears to be an ideal candidate for antitumor therapy. However, despite initial interest in its clinical applications, only a limited number of high-quality trials have been conducted thus far. Aclarubicin has primarily been evaluated as an induction therapy in acute myeloid and lymphoblastic leukemia. Studies have indicated that aclarubicin may hold significant promise for combination therapies with other anticancer drugs, although further research is needed to confirm its potential. This paper provides an in-depth exploration of aclarubicin's diverse mechanisms of action, its pharmacokinetics, potential toxicity, and the clinical trials in which it has been investigated.
阿克拉霉素(阿克拉霉素 A)是一种蒽环类抗肿瘤抗生素,具有多方面的抗肿瘤活性机制。作为第二代药物,与多柔比星或柔红霉素等标准蒽环类药物相比,它具有许多优势,这使其有可能成为抗肿瘤治疗中的一种潜在重磅药物。阿克拉霉素的主要作用机制包括抑制两种拓扑异构酶、抑制肿瘤侵袭过程、产生活性氧、抑制糜蛋白酶样活性、影响顺铂降解和抑制血管生成。因此,阿克拉霉素似乎是抗肿瘤治疗的理想候选药物。然而,尽管最初对其临床应用感兴趣,但迄今为止仅进行了有限数量的高质量试验。阿克拉霉素主要作为急性髓细胞性白血病和淋巴母细胞性白血病的诱导治疗进行评估。研究表明,阿克拉霉素与其他抗癌药物联合治疗可能具有很大的潜力,但需要进一步研究来证实其潜力。本文深入探讨了阿克拉霉素的多种作用机制、药代动力学、潜在毒性以及已进行的临床试验。